Neuropharmacology and analgesiaProlonged analgesic effect of amitriptyline base on thermal hyperalgesia in an animal model of neuropathic pain

The best analgesic drugs for neuropathic pain have a long duration of action, can be given via multiple routes, and can be used preemptively. We evaluated the antinociceptive effects and duration of action of subcutaneously injected amitriptyline base (AMT-Base) (in oil). A plantar test in a spinal nerve ligation (SNL) model of neuropathic pain in rats showed that typical amitriptyline HCl (AMT-HCl) (in saline) and AMT-Base had a significant dose-dependent antinociceptive effect: the antinociceptive duration of a single 100 μmol/kg injection of AMT-HCl was 5 h and of AMT-Base was 24 h when given 7 days after a SNL, and of a single 200 μmol/kg injection of AMT-Base was 39 days when given 1 h before and 4 days when given 7 days after a SNL. The post-ligation antinociceptive duration of AMT-Base was 4.8 times that of AMT-HCl, but the duration of preemptive (pre-ligation) AMT-Base treatment was 9.7 times that of AMT-Base. We can conclude that preemptive amitriptyline base provides long-lasting antinociception for neuropathic pain experimentally.